Direct interaction of proteoglycan macrophage colony-stimulating factor and
basic fibroblast growth factor
S Suzu, F Kimura, M Yamada, N Yanai, T Kawashima, N Nagata and K Motoyoshi
Biochemical Research Laboratory, Morinaga Milk Industry Co, Ltd, Kanagawa,
Japan.
The proteoglycan form of macrophage colony-stimulating factor (PG-M- CSF),
but not M-CSF with a molecular weight of 85 kD (85-kD M-CSF), bound to
immobilized basic fibroblast growth factor (bFGF), and, conversely, bFGF
bound to immobilized PG-M-CSF, but not to the 85-kD M- CSF. PG-M-CSF has an
additional amino acid sequence at its carboxyl terminus (part of a
precursor sequence that is removed in 85-kD M-CSF by proteolytic
processing) and it has one or two chondroitin sulfate glycosaminoglycan
chains at the carboxyl terminus. Enzymatic removal of the chondroitin
sulfate chain from PG-M-CSF had no effect on the binding between PG-M-CSF
and bFGF. Ligand blotting analysis with radioiodinated bFGF showed that
bFGF specifically bound to the polypeptide that corresponded to the
carboxyl terminus of PG-M-CSF and was produced in Escherichia coli
transfected with its gene. The exogeneous addition of heparan sulfate,
which has strong affinity for bFGF, efficiently inhibited the binding
between PG-M-CSF and bFGF. These results show that PG-M-CSF binds bFGF
through its carboxyl terminal peptide and that the binding sites for
PG-M-CSF and heparan sulfate on bFGF are located close together. PG-M-CSF
also significantly reduced the mitogenic action of bFGF on Balb/c 3T3 mouse
fibroblastic cells. Therefore, we conclude that PG-M-CSF not only binds
bFGF, but also neutralizes the activity of the growth factor.
Volume 83,
Issue 11,
pp. 3113-3119,
06/01/1994
Copyright © 1994 by The American Society of Hematology
